Ab initio study of electron transport in dry poly(G)-poly(C) A-DNA strands

The bias-dependent transport properties of short poly(G)-poly(C) A-DNA strands attached to Au electrodes are investigated with first principles electronic transport methods. By using the non- equilibrium Green's function approach combined with self-interaction corrected density functional theory, we calculate the fully self-consistent coherent I-V curve of various double-strand polymeric DNA fragments. We show that electronic wave-function localization, induced either by the native electrical dipole and/or by the electrostatic disorder originating from the first few water solvation layers, drastically suppresses the magnitude of the elastic conductance of A-DNA oligonucleotides. We then argue that electron transport through DNA is the result of sequence-specific short-range tunneling across a few bases combined with general diffusive/inelastic processes.Comment: 15 pages, 13 figures, 1 tabl

Modelling allosteric regulation for prediction of flux control in the central carbon metabolism of E. coli

Rational strain design is a fundamental step in the development of microbial cell factories. Multiple genetic manipulations are often required in order to redirect the metabolic flux towards a product of industrial interest. Most manipulation targets are focused on central carbon metabolism, which provides the molecular precursors and the energy required for other biochemical pathways. However, the complex regulation of those pathways is still not completely unraveled. Recent studies have shown that central carbon metabolism is mostly regulated at post-transcriptional levels. In this work, we explore the role of allosteric regulation in the control of metabolic fluxes. We begin by expanding a metabolic network reconstruction of the central carbon metabolism of E. coli with allosteric interaction information from relevant databases. This model is used to integrate a multi-omic dataset for this organism. We analyze the coordinated changes in enzyme, metabolite and flux levels between multiple experimental conditions, and observe cases where allosteric regulators have a major contribution in the metabolic flux changes. We then develop a method for systematic prediction of potential cases of allosteric control for given metabolic perturbations. This is a valuable approach for predicting coordinated flux changes that would not be predicted with a purely stoichiometric model representation.BioInd - Biotechnology and Bioengineering for improved Industrial and Agro-Food processes, REF. NORTE-07-0124-FEDER-00002

Transcriptional vs post-transcriptional regulation of the central carbon metabolism of E. coli

Transcriptomics data are currently one of the most available types of large-scale biological data. A large number of methods have been developed to improve constraint-based simulations using these data. We recently performed a systematic comparison of these methods and observed that, at least for central carbon metabolism, there is no significant improvement in the prediction of flux distributions when gene expression data is used. These results are consistent with recent studies, in different organisms, showing that central carbon metabolism is predominantly regulated at post-transcriptional levels. Central carbon metabolism provides the precursors for the production of multiple compounds used in industrial biotechnology. Hence, it is the main target for intervention in most rational strain design strategies. However, its complexity is still not completely understood. In this work, we analyze the role of allosteric regulation, one of the main mechanisms of post-transcriptional regulation, for the control of central carbon metabolism. We extend a model of central carbon metabolism of E. coli with allosteric interactions, revealing a hidden topology in metabolic networks. We use this model to integrate a multi-omic dataset containing transcript, protein, flux and metabolite levels to further dissect the contribution of different types of regulation for metabolic flux control in these central pathways. Situations of predominant allosteric control could be identified, highlighting the importance of this kind of regulation in central carbon metabolism

Modeling the contribution of allosteric regulation for flux control in the central carbon metabolism of E. coli

Redesign of microbial metabolism is a critical step in biotechnology for the production of industrially relevant compounds. Central carbon metabolism provides the energy and building blocks required for cellular growth and synthesis of the desired byproducts and, consequently, it is the main target for intervention in most rational strain design approaches. However, the complexity of central carbon metabolism is still not completely understood. Recent studies in different organisms show that flux control in central carbon metabolism is predominantly regulated by non-transcriptional mechanisms, leaving post-translational modifications, allosteric regulation, and thermodynamics as main candidates. In this work, we extend a model of central carbon metabolism of E.coli with allosteric interactions in order to reveal a hidden topology in metabolic networks. We use this model to integrate a multi-omic dataset containing transcript, protein, flux and metabolite levels to further dissect and analyze the contribution of allosteric regulation for metabolic flux control

Alimentos funcionais : uma área estratégica para a BIOTEMPO

A BIOTEMPO – Consultoria em Biotecnologia, Lda. é uma empresa de base tecnológica que surgiu como resultado de um spin-off da Universidade do Minho. A sua actividade centra-se na prestação de serviços de consultoria e promoção de actividades de investigação e desenvolvimento. Actualmente, a BIOTEMPO participa em vários projectos de I&D, alguns dos quais são executados em parceria com empresas e universidades nacionais. No âmbito da sua Unidade de Biotecnologia Alimentar e Farmacêutica a BIOTEMPO tem-se dedicado ao desenvolvimento de novas tecnologias para a produção de ingredientes para alimentos funcionais, tendo elegido esta área como estratégica para o desenvolvimento da empresa

Design of a biosynthetic pathway for curcumin production in Escherichia coli

Curcumin is the yellow pigment from turmeric, a well known culinary spice produced from the herb Curcuma longa. Research over the last years has shown that curcumin presents a wide range of pharmacological effects, including anti-inflammatory, anti-oxidant and anticarcinogenic activity. Given its potential application in cancer treatment, there is an interest for industrial production of this natural compound. This work consists on a synthetic biology approach for the design of a heterologous pathway for curcumin synthesis in Escherichia coli, a widely used microbe in industrial biotechnology. Using pathway databases and literature research we have selected the best gene candidates for heterologous expression of a curcumin synthesis pathway in E. coli. The DNA sequences for these genes were retrieved from public databases and can be readily synthesized for insertion into the host using molecular biology techniques. The inclusion of this pathway in a recent genome-scale reconstruction of the metabolism of E. coli has enabled the in silico analysis of the production capabilities for this host. We have analysed the theoretical production yields and biomass growth under different experimental conditions. Using this model we have also searched for potential gene knockouts that partially redirect the metabolic flux to the heterologous pathway without compromising cellular growth. In overall, the methods used in this work allow the selection of the most suitable combination of experimental conditions and genetic manipulations for the design of an efficient biosynthetic pathway for curcumin production in E.coli

Revisiting Clifford algebras and spinors III: conformal structures and twistors in the paravector model of spacetime

This paper is the third of a series of three, and it is the continuation of math-ph/0412074 and math-ph/0412075. After reviewing the conformal spacetime structure, conformal maps are described in Minkowski spacetime as the twisted adjoint representation of the group Spin_+(2,4), acting on paravectors. Twistors are then presented via the paravector model of Clifford algebras and related to conformal maps in the Clifford algebra over the lorentzian R{4,1}$ spacetime. We construct twistors in Minkowski spacetime as algebraic spinors associated with the Dirac-Clifford algebra Cl(1,3)(C) using one lower spacetime dimension than standard Clifford algebra formulations, since for this purpose the Clifford algebra over R{4,1} is also used to describe conformal maps, instead of R{2,4}. Although some papers have already described twistors using the algebra Cl(1,3)(C), isomorphic to Cl(4,1), the present formulation sheds some new light on the use of the paravector model and generalizations.Comment: 17 page

Modeling formalisms in systems biology

Systems Biology has taken advantage of computational tools and high-throughput experimental data to model several biological processes. These include signaling, gene regulatory, and metabolic networks. However, most of these models are specific to each kind of network. Their interconnection demands a whole-cell modeling framework for a complete understanding of cellular systems. We describe the features required by an integrated framework for modeling, analyzing and simulating biological processes, and review several modeling formalisms that have been used in Systems Biology including Boolean networks, Bayesian networks, Petri nets, process algebras, constraint-based models, differential equations, rule-based models, interacting state machines, cellular automata, and agent-based models. We compare the features provided by different formalisms, and discuss recent approaches in the integration of these formalisms, as well as possible directions for the future.Research supported by grants SFRH/BD/35215/2007 and SFRH/BD/25506/2005 from the Fundacao para a Ciencia e a Tecnologia (FCT) and the MIT-Portugal Program through the project "Bridging Systems and Synthetic Biology for the development of improved microbial cell factories" (MIT-Pt/BS-BB/0082/2008)